DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU

Information source: Stanford University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hyperactive Delirium; Mixed Delirium

Intervention: Valproic Acid (Drug); Placebo (Drug); Haloperidol (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Stanford University

Official(s) and/or principal investigator(s):
Yelizaveta Sher, M.D., Principal Investigator, Affiliation: Stanford University
Jose R Maldonado, M.D., Study Director, Affiliation: Stanford University

Overall contact:
Shengchun Wang, Ph.D, Phone: 5183342513, Email: swang6@stanford.edu


Delirium is the most often encountered psychiatric diagnosis in the general hospital, with incidence up to 85% in the intensive care unit (ICU) setting and with significant consequences on patients' morbidity and mortality. Currently, although not FDA approved, antipsychotics are often considered the first-line pharmacological treatment. However, there can be limitations to their use, including side effects or lack of efficacy. Valproic acid (VPA) is one of the alternatives at times used in such patients which from limited case series data appears to be helpful and tolerated. VPA can provide relief from agitation that poses a threat to the safety and recovery of the patient. Moreover, mechanistically it addresses the neurochemical and cellular abnormalities inherent in delirium (it has NMDA-antagonist, anti-dopaminergic, GABAergic,anti-inflammatory, anti-apoptotic, and histone deacetylase inhibitor properties, among others). The purpose of this study is to evaluate the efficacy and tolerability of the VPA in the first known to us randomized controlled trial.

Clinical Details

Official title: Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Time to delirium resolution

Secondary outcome:

Use of as needed anti-psychotic agent

Mortality rate

Side effects from medications (Side effects from VPA (LFT increase, platelet decrease, bleeding), haloperidol side effects (QTc prolongation, extrapyramidal side effects)

Intensity of delirium (measured by ICDCS delirium severity scale)

Length of ICU stay

Length of hospital stay

Detailed description: The investigators plan to investigate the efficacy and tolerability of scheduled VPA as compared to placebo with as needed basis (PRN) haloperidol (as a back-up in both arms) for treatment of hyperactive or mixed delirium. Patients will be randomized to scheduled VPA or placebo (normal saline) and both arms will have flexible PRN dosing of haloperidol. Thus, the investigators plan to learn the time to delirium resolution in patients treated with VPA versus placebo; percentage of patients responding to VPA versus placebo; tolerability of VPA versus placebo. If addition of scheduled VPA proves to shorten time to delirium resolution as compared to placebo, lead to less use of haloperidol, and/or have fewer side effects, it would provide a very important addition to our limited evidence-based repertoire of delirium treatment. Moreover, this pilot study would then pave the way for the bigger randomized control trial powered to detect its effect size.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- patients 18 years of age and older

- admitted to surgical ICU

- diagnosed with hyperactive or mixed delirium

Exclusion Criteria:

- hypoactive delirium

- primary team does not think patient is appropriate to participate

- no oral access (PO or NGT)

- non-English speaking

- contraindication to study medications

- pregnant women or woman of child-bearing age not on documented contraception

- QTc = or greater than 480

- hepatic dysfunction

- decreased platelets or platelet dysfunction

- bleeding disorder, current major bleeding

- history of NMS, epilepsy, or PD

- diagnosis of schizophrenia, bipolar disorder or schizoaffective disorder

- on warfarin or carbapenems

- delirium due to alcohol withdrawal

- treated with antipsychotics for more than 48 hours prior to study enrollment.

Locations and Contacts

Shengchun Wang, Ph.D, Phone: 5183342513, Email: swang6@stanford.edu

Stanford Hospital and Clinics, Stanford, California 94305, United States; Recruiting
Shengchun Wang, Ph.D, Phone: 518-334-2513, Email: swang6@stanford.edu
Additional Information

Starting date: January 2015
Last updated: February 25, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017